1. Field of the Invention
The present invention relates to a process for preparing .sup.13 C-labelled compounds specifically labelled with .sup.13 C in a specific carbon position.
2. Description of the Prior Art
.sup.13 C-labelled fructose 6-phosphate, for example, is known to be prepared by a chemical synthesis process, in which a large number of reaction steps are required in order to obtain .sup.13 C-labelled fructose 6-phosphate labelled with a specifically positioned .sup.13 C because fructose has four asymmetric carbon atoms to provide 16 different optical isomers, resulting in obtaining a product having not so high optical purity.
Japanese Patent Application Laid-Open No. 130692/87 discloses a process for producing isotope labelled biochemicals which comprises cultivating a methylotrophic microorganism in a nutrient medium containing a growth carbon source comprising a .sup.13 C.sub.1 -compound.
Japanese Patent Application Laid-Open No. 130692/87 discloses a bioconversion process which comprises cultivating a methylotrophic microorganism (or cell extract thereof) in a nutrient medium containing an assimilable C.sub.n -compound and a .sup.13 C.sub.1 -compound to produce an accumulated quantity of .sup.13 C-labelled C.sub.n+1 -condensation product, wherein n is an integer with a value of at least 2.
Japanese Patent Application Laid-Open No. 130692/87 discloses on page 5, right upper column, lines 8-12, that the term "ribulose monophosphate pathway" (RMP) as employed herein refers to the biochemical cycle in which three molecules of formaldehyde are condensed to produce either one molecule of pyruvate or one molecule of dihydroxyacetone phosphate, and further teaches on page 7, left lower column, line 16 to right lower column, line 5, that hexulose 6-phosphate is the product of hexulose phosphate synthase activity and that hexulose phosphate isomerase converts hexulose 6-phosphate to glucose 6-phosphate.
However, Japanese Patent Application Laid-Open No. 130692/87 neither teaches nor suggests process for preparing .sup.13 C-labelled fructose 6-phosphate or .sup.13 C-labelled glucose 6-phosphate specifically labelled with .sup.13 C in a carbon position C-1 from ribose 5-phosphate and .sup.13 C-labelled methanol or .sup.13 C-labelled formaldehyde in the presence of a specific series of enzymes.
Japanese Patent Application Laid-Open No. 130692/87 discloses, in Example, preparation of the exopolysaccharide containing .sup.13 C-glucose as a main constituent by carrying out fermentation using .sup.13 C-methanol as a growth carbon source, resulting in producing .sup.13 C-glucose uniformly labelled with .sup.13 C and in being impossible to obtain .sup.13 C-labelled glucose specifically labelled with .sup.13 C in a carbon position C-1.
The use of .sup.13 C-labelled compounds specifically labelled with .sup.13 C in a specific carbon position in the case of studies on a biological energy metabolism pathway by use of nuclear magnetic resonance apparatus, mass spectrometer, etc. makes it possible to provide useful qualitative and quantitative informations more than in the case of use of compounds uniformly labelled with .sup.13 C, .sup.14 C-labelled compounds, and the like, resulting in that the .sup.13 C-labelled compounds specifically labelled with .sup.13 C in a specific carbon position are applicable to various fields ranging from studies on biological reactions to medical services and development of an industrially advantageous process for the preparation thereof is highly demanded.
For example, fructose 6-phosphate or glucose 6-phosphate is a metabolic intermediate in the glycolitic pathway and is useful for studies of the biological energy metabolism pathway, and .sup.13 C-labelled fructose 6-phosphate or .sup.13 C-labelled glucose 6-phosphate specifically labelled with .sup.13 C in a specific carbon position is preferable on tracing a conversion process of fructose 6-phosphate or glucose 6-phosphate in vivo by use of mass spectrometer, nuclear magnetic resonance apparatus, etc. compared with ones uniformly labelled with .sup.13 C, resulting in that development of an industrially advantageous process for the preparation thereof is highly demanded.